Numerical solutions of a generalized theory for macroscopic capillarity.
A recent macroscopic theory of biphasic flow in porous media [R. Hilfer, Phys. Rev. E 73, 016307 (2006)] has proposed to treat microscopically percolating fluid regions differently from microscopically nonpercolating regions. Even in one dimension the theory reduces to an analytically intractable set of ten coupled nonlinear partial differential equations. This paper reports numerical solutions for three different initial and boundary value problems that simulate realistic laboratory experiments. All three simulations concern a closed column containing a homogeneous porous medium filled with two immiscible fluids of different densities. In the first simulation the column is raised from a horizontal to a vertical orientation inducing a buoyancy-driven fluid flow that separates the two fluids. In the second simulation the column is first raised from a horizontal to a vertical orientation and subsequently rotated twice by 180 degrees to compare the resulting stationary saturation profiles. In the third simulation the column is first raised from horizontal to vertical orientation and then returned to its original horizontal orientation. In all three simulations imbibition and drainage processes occur simultaneously inside the column. This distinguishes the results reported here from conventional simulations based on existing theories of biphasic flows. Existing theories are unable to predict flow processes where imbibition and drainage occur simultaneously. The approximate numerical results presented here show the same process dependence and hysteresis as one would expect from an experiment.


Recognition and prevention of child abuse in the child with disability.
Children with disabilities (CWD) are victims of abuse more frequently than children in the general population. The features of their underlying conditions make it more difficult to detect abuse and on occasion can be mistaken for abuse. Thus, the expertise of the clinical geneticist is often vital to properly identifying maltreatment in this vulnerable population. The purpose of this article is to review the magnitude of abuse in the population of CWD, to identify the aggravating factors, and to suggest practice changes in order to both diagnose and reduce the likelihood of abuse in CWD.


An anomalous portal vein crossing the lesser sac and ending at the upper part of ductus venosus.
In serial sagittal sections of a fetus on week 9 (crown-rump length, 36 mm), we incidentally found absence of the usual portal vein through the hepatoduodenal ligament. Instead, an anomalous portal vein originated behind the pancreatic body, crossed the lesser sac and merged with the upper part of the ductus venosus. During the course across the lesser sac, the vein provided a deep notch of the liver caudate lobe (Spiegel's lobe). The hepatoduodenal ligament contained the hepatic artery, the common bile duct and, at the right posterior margin of the ligament, and a branch of the anomalous portal vein which communicated with the usual right branch of the portal vein at the hepatic hilum. The umbilical portion of the portal vein took a usual morphology and received the umbilical vein and gave off the ductus venosus. Although it seemed not to be described yet, the present anomalous portal vein was likely to be a persistent left vitelline vein. The hepatoduodenal ligament was unlikely to include the left vitelline vein in contrast to the usual concept.


Streptococcus pasteurianus septicemia.
Streptococcus pasteurianus is part of the normal flora of the intestine. It has also been isolated from various infection sites. However, to date it has not been reported as a cause of fulminant septicemia and death. We report the post-mortem findings in a splenectomized hemophiliac patient with cirrhosis and concurrent human immunodeficiency virus (HIV), hepatitis B and hepatitis C infections.


[Minimally invasive technologies of lithotripsy and antegrade hydraulic lithoextraction in complex treatment of choledocholithiasis].
To evaluate the effectiveness of minimally invasive technologies of lithotripsy and hydraulic antegrade lithoextraction in complex treatment of choledocholithiasis. In the main group, 74 patients with choledocholithiasis underwent complex treatment with minimally invasive lithotripsy and hydraulic antegrade lithoextraction. In the control group, 177 patients with choledocholithiasis complicated by obstructive jaundice underwent complex treatment without minimally invasive lithotripsy and hydraulic antegrade lithoextraction. Both groups were characterized by significant decrease of serum bilirubin, markers of cytolysis and cholestasis with regression of clinical manifestations of obstructive jaundice. At the same time, early and delayed postoperative complications were significantly more common in the control group. Most of these complications accounted for interventions through laparotomy such as external drainage of the common bile duct and hepaticojejunostomy. There were no similar procedures in the main group due to the use of minimally invasive technologies of lithotripsy and antegrade hydraulic lithoextraction. Minimally invasive lithotripsy and antegrade hydraulic lithoextraction are safe alternatives to traditional methods of lithoextraction and can be recommended in case of ineffective laparoscopic and retrograde endoscopic lithoextraction.


Viral infection can induce the production of autoantibodies.
To review the current literature and summarize the main principles found between viral infections and the subsequent production of autoantibodies. We concentrate on recent findings involving three viral agents, one of which is Epstein-Barr virus, which has been associated with many autoimmune diseases and is classically considered to induce systemic lupus erythematosus. As we will discuss, this occurs through molecular mimicry between Epstein-Barr virus nuclear antigen 1 and lupus-specific antigens such as Ro, La or dsDNA, through induction of Toll-like receptor hypersensitivity by Epstein-Barr virus latent membrane protein 2A or by creating immortal B and T cells by loss of apoptosis. Hepatitis B virus was found to share amino acid sequences with different autoantigens. Tissue damage and the release of intracellular components is just another example of the autoantibody production caused by this virus. Cytomegalovirus has often been controversially associated with several autoimmune diseases and, although is the least understood viral infection of the three, appears to be somewhat suspicious. Understanding the infectious origin of autoimmune diseases is important as we aim to identify high-risk patients and disrupt this process with vaccines or other medications, ultimately delaying or even preventing the evolution of autoimmune diseases.


[Macrocytic megaloblastic anaemia in a patient with Helicobacter pylori infection].
We present 62 yrs old patient in whom megaloblastic anaemia due to vitamin B12 depletion was caused by Helicobacter pylori infection. An eradication treatment with the vitamin B12 supplementation within 7 days resulted in withdrawal of the abnormalities in the blood smear. The inflammation of gastric mucosa with intestine metaplasia is still observed. According to the letters these changes may persist up to 2-3 years after treatment ending.


Self-Assembled Pico-Liter Droplet Microarray for Ultrasensitive Nucleic Acid Quantification.
Nucleic acid detection and quantification technologies have made remarkable progress in recent years. Among existing platforms, hybridization-based assays have the advantages of being amplification free, low instrument cost, and high throughput, but are generally less sensitive compared to sequencing and PCR assays. To bridge this performance gap, we developed a quantitative physical model for the hybridization-based assay to guide the experimental design, which leads to a pico-liter droplet environment with drastically enhanced performance and detection limit several order above any current microarray platform. The pico-liter droplet hybridization platform is further coupled with the on-chip enrichment technique to yield ultrahigh sensitivity both in terms of target concentration and copy number. Our physical model, taking into account of molecular transport, electrostatic intermolecular interactions, reaction kinetics, suggests that reducing liquid height and optimizing target concentration will maximize the hybridization efficiency, and both conditions can be satisfied in a highly parallel, self-assembled pico-liter droplet microarray that produces a detection limit as low as 570 copies and 50 aM. The pico-liter droplet array device is realized with a micropatterned superhydrophobic black silicon surface that allows enrichment of nucleic acid samples by position-defined evaporation. With on-chip enrichment and oil encapsulated pico-liter droplet arrays, we have demonstrated a record high sensitivity, wide dynamic range (6 orders of magnitude), and marked reduction of hybridization time from >10 h to <5 min in a highly repeatable fashion, benefiting from the physics-driven design and nanofeatures of the device. The design principle and technology can contribute to biomedical sensing and point-of-care clinical applications such as pathogen detection and cancer diagnosis and prognosis.


Unexpected effects of methylphenidate in attention-deficit/hyperactivity disorder reflect decreases in core/secondary symptoms and physical complaints common to all children.
Abstract Hypotheses concerning unexpected, psychostimulant-related effects reported in previous studies were examined by separating behavioral/physical complaints highly specific to methylphenidate (MPH) from those that (a) may mimic core/secondary symptoms of the disorder, or (b) are commonly reported by unmedicated children in the general population. Sixty-five children with attention-deficit/hyperactivity disorder (ADHD) participated in a double-blind, placebo-controlled, within-subject (crossover) experimental design and received a placebo and four MPH doses in counterbalanced order following baseline assessment. Behavioral and physical complaints were significantly higher under baseline relative to placebo and the four immediate-release MPH conditions (5 mg, 10 mg, 15 mg, and 20 mg) across three symptom categories: ADHD core/secondary symptoms; symptoms commonly reported in the general population, including unmedicated children with ADHD; and symptoms highly specific to MPH. No significant differences were found among active drug conditions. Past unexpected findings of psychostimulant effects in ADHD may be due to the inclusion of scale items that reflect core/secondary features of ADHD and normally occurring behavioral/physical complaints in children.


Genomic Approaches Are Improving Taxonomic Representation in Genetic Studies of Speciation.
Until recently, our understanding of the genetics of speciation was limited to a narrow group of model species with a specific set of characteristics that made genetic analysis feasible. Rapidly advancing genomic technologies are eliminating many of the distinctions between laboratory and natural systems. In light of these genomic developments, we review the history of speciation genetics, advances that have been gleaned from model and non-model organisms, the current state of the field, and prospects for broadening the diversity of taxa included in future studies. Responses to a survey of speciation scientists across the world reveal the ongoing division between the types of questions that are addressed in model and non-model organisms. To bridge this gap, we suggest integrating genetic studies from model systems that can be reared in the laboratory or greenhouse with genomic studies in related non-models where extensive ecological knowledge exists.


Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate.
Lipooligosaccharide (LOS) is a major surface component of Moraxella catarrhalis and a possible virulence factor in the pathogenesis of human infections caused by this organism. The presence of LOS on the bacterium is an obstacle to the development of vaccines derived from whole cells or outer membrane components of the bacterium. An lpxA gene encoding UDP-N-acetylglucosamine acyltransferase responsible for the first step of lipid A biosynthesis was identified by the construction and characterization of an isogenic M. catarrhalis lpxA mutant in strain O35E. The resulting mutant was viable despite the complete loss of LOS. The mutant strain showed significantly decreased toxicity by the Limulus amebocyte lysate assay, reduced resistance to normal human serum, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. Importantly, the mutant elicited high levels of antibodies with bactericidal activity and provided protection against a challenge with the wild-type strain. These data suggest that the null LOS mutant is attenuated and may be a potential vaccine candidate against M. catarrhalis.


Theoretical basis for the detection of general-base catalysis in the presence of predominating hydroxide catalysis.
The detection of general-base catalysis in the presence of predominating specific-base catalysis in aqueous buffer solutions is examined for various relationships between k0cat and k0OH, the bimolecular rate constants for general-base and hydroxide-ion attack. The three experimental variables that affect the detection of buffer-base catalysis are the type of buffer, conjugate-acid concentration, and ionic strength. Various buffers used in pharmaceutical kinetic studies are considered, and it is concluded that buffers with high Ka values favor detection. Additionally, high conjugate-acid concentrations and ionic strengths appear to optimize the detection of general-base catalysis.


Coronary CT angiography: State of the art.
Coronary computed tomography (CT) angiography has been recognized as the most rapidly developed imaging technique in the diagnosis of coronary artery disease due to the emergence and technological advances in multislice CT scanners. Coronary CT angiography has been confirmed to demonstrate high diagnostic and predictive value in coronary artery disease when compared to invasive coronary angiography. However, it suffers from high radiation dose which raises concerns in the medical field. Various dose-reduction strategies have been proposed with effective outcomes having been achieved to reduce radiation exposure to patients. This article provides an introduction and overview of the series of articles that will focus on each particular topic related to coronary CT angiography.


Using the Delphi Method to Identify Risk Factors Contributing to Adverse Events in Residential Aged Care Facilities.
This study aimed to identify risk factors associated with adverse events in residential aged care facilities in China. After compiling a list of risk factors for adverse events generated from in-depth interviews with managers of residential aged care facilities, a three-round Delphi method was used to reach consensus. The synthesized risk factors were presented on a Likert scale to the expert panelists three times to validate their responses. The list identified 67 items as risk factors for adverse events, attached to four first-level indexes (ie, environmental facility, nursing staff, older adults' characteristics, and management factors). The experts' authority coefficient was 0.87. The positive coefficients were 82.76%, 91.67%, and 100%, and the coordination coefficients were 0.154, 0.297, and 0.313 in the first, second, and third rounds, respectively. Using a Delphi method, this study established a consensus on risk factors contributing to adverse events and developed a risk assessment grade for use in future aged care practice and research. The resulting list is useful in prioritizing risk-reduction activities and assessing intervention or education strategies for preventing adverse events in residential aged care facilities. This study fills the gap in risk identification in the Chinese residential aged care system to ensure provision of best-practice care to this vulnerable population. Nursing staff and management factors at the top of the list are not only the most common causes of adverse events but also the core elements in creating a secure and error-free environment. This list was intended to support predictive and prevention-oriented decision-making by managers and nursing supervisors to reduce preventable adverse events.


The frequency, related cause of disease, and treatment of hepatitis B virus infection: A systematic review and meta-analysis in Iran.
Hepatitis B virus (HBV) is one of the most dreadful viruses causing high mortality rates and serious damages to hepatocytes. The aim of this study was to assess the frequency, related causes/risk factors, and treatments of HBV infection in Iran by systematic review and meta-analysis. The data were obtained by a literature search in the PubMed, Scopus, SID, and Web of Sciences databases. Keywords included prevalence, risk factors, causes, treatment, and HBV. The Persian equivalents of these keywords were also searched. The time span included 2004 to2021. The Q and I 2 statistics were used to check heterogeneity among studies. The data were analyzed using Stata (version 14). The frequencies of HBV infection and its pharmaceutical therapy were P = 6% (95% confidence interval [CI]: 4-9, I 2 = 95.2%, P < 0.001) and 19% (95% CI: 18%-30%, I 2 = 98.9%, P < 0.001), respectively. The most common risk factors/causes of HBV were narcotic consumption, blood-related factors, and transmission from infected individuals with the respective frequencies of 27% (95% CI: 16%-38%, I 2 = 88.7%, P < 0.001), 32% (95% CI: 11%-53%, I 2 = 99.8%, P < 0.001), 25% (95% CI: 10%-41%, I 2 = 99.3%, P < 0.001), and 15% (95% CI: 7%-22%, I 2 = 98.4%, P < 0.001), respectively. The most important causes of HBV infection were transmission from infected people, narcotic consumption, and blood-related factors. The main therapeutic intervention for HBV was pharmaceutical therapy.


[The role of similarity and category in confirmation judgement of category-based induction: an examination of the similarity-coverage model].
Induction is called category-based induction if its premises and conclusion are of the form "All members of a category C have property P." Osherson, Smith, Wilkie, Lopez, and Shafir (1990) advanced similarity-coverage model. But their data from a quantitative test of specific induction did not necessarily support the model. Three experiments investigate whether their modeling of similarity and coverage was not valid or their experiments were not valid. The following results were obtained. Coverage did not affect confirmation judgement in premise-variation type induction which Osherson et al. (1990) dealt with, and coverage effect was verified in conclusion-variation type induction which is more everyday and needs less processing load. In the latter case, coverage had to be weighted by typicality of conclusion in an inclusive category. And when mixed inductions were included, confirmation judgement was based not on coverage but on a belonging relation to an upper category and similarity between premise categories and a conclusion category.


SCN5A Genetic Polymorphisms Associated With Increased Defibrillator Shocks in Brugada Syndrome.
Brugada syndrome (BrS) is an inherited primary arrhythmia disorder leading to sudden cardiac arrest. SCN5A, encoding the α-subunit of the cardiac sodium channel (Nav1.5), is the most common pathogenic gene of BrS. An implantable cardioverter defibrillator (ICD) is the standard treatment for secondary prevention. This study aimed to evaluate association of the SCN5A variant with this cardiac conduction disturbance and appropriate ICD shock therapy in Thai symptomatic BrS patients with ICD implants. Symptomatic BrS patients diagnosed at university hospital were enrolled from 2008 to 2011. The primary outcome of the study was an appropriate ICD shock defined as having non-pacing-associated ICD shock after the occurrence of ventricular tachycardia or ventricular fibrillation. Associations between SCN5A polymorphisms, cardiac conduction disturbance, and potential confounding factors associated with appropriate ICD shock therapy were analyzed. All 40 symptomatic BrS patients (median age, 43 years) with ICD implantations were followed for 24 months. There were 16 patients (40%) who had the appropriate ICD shock therapy after ICD treatment. An independent factor associated with appropriate ICD shock therapy was SCN5A-R1193Q with an adjusted hazard ratio of 10.550 (95% CI, 1.631-68.232). SCN5A-R1193Q is associated with cardiac conduction disturbances. It may be a genetic marker associated with ventricular arrhythmia leading to appropriate ICD shock therapy in symptomatic BrS patients with ICD treatment. Because of the small sample size of study population and the appropriate ICD shock outcome, further large studies are needed to confirm the results of this study.


Structural insight into the binding of C60-derivatives with enoyl-pyruvate transferase from Helicobacter pylori.
Helicobacter pylori (H. pylori) is a human pathogen associated with acute gastritis and peptic ulcer. The MurA enzyme is an important drug target for the identification of ligands with improved efficacy and acceptable pharmaco-kinetic properties. We developed a homology model of H. Pylori MurA followed by refinement and molecular dynamics (MD) simulations. A total of 16 C60-derivatives were docked and its docking score were compared. Some of the known inhibitors were also similarly characterized and compared. Results show that five out of the sixteen C60-derivatives have good binding score. The MMPBSA analysis for the top five C60- derivatives shows good binding energy. This study reports the interaction patterns of selected C60 derivatives and MurA enzyme towards fullerene-based drug discovery.


Oyster-based national mapping of trace metals pollution in the Chinese coastal waters.
To investigate the distribution and variability of trace metal pollution in the Chinese coastal waters, over 1000 adult oyster individuals were collected from 31 sites along the entire coastline, spanning from temperate to tropical regions (Bohai Sea, Yellow Sea, East China Sea and South China Sea), between August and September 2015. Concentrations of macroelements [sodium (Na), potassium (K), calcium (Ca), magnesium (Mg) and phosphorus (P)] and trace elements [cadmium (Cd), copper (Cu), zinc (Zn), nickel (Ni), lead (Pb), chromium (Cr), silver (Ag), and titanium (Ti)] in these oysters were concurrently measured and analyzed. The results showed high Ti, Zn and Cu bioaccumulation in oysters from Guangdong (South China Sea) and Zhejiang (East China Sea). Oysters at Nanji Island (Wenzhou) and Daya Bay (Huizhou) accumulated significantly high concentrations of Ni and Cr. The elements in these oysters were several times higher than the national food safety limits of China. On the other hand, the present study found that normalization of metals by salinity (Na) and nutrient (P) could reflect more details of metal pollution in the oysters. Biomonitoring of metal pollution could benefit from incorporating the macroelement calibration instead of focusing only on the total metal concentrations. Overall, simultaneous measurement of macroelements and trace metals coupled with non-linear analysis provide a new perspective for revealing the underlying mechanism of trace metal bioavailability and bioaccumulation in marine organisms.


Neuropsychological differences between violent and nonviolent adolescents.
Administered the MMPI and elements of a neuropsychological assessment battery to 40 violent and 40 nonviolent adolescent males (M = 14.6 years). Multivariate analysis showed significant differences between groups on neuropsychological tests, but not on the MMPI. Discriminant function analysis indicated that the neuropsychological assessment had greater power to predict group membership of violent and nonviolent Ss than did the MMPI. The results are consistent with the hypothesis that organic impairment contributes to the impulse dyscontrol and associated violent behavior seen in some delinquent adolescents.


Synchronous Induction of Meiosis in the Fission Yeast Schizosaccharomyces pombe.
In fission yeast Schizosaccharomyces pombe, initiation of meiosis is repressed by Pat1 kinase. This protocol describes how ectopic inactivation of the temperature-sensitive Pat1-114 kinase in G1-arrested h- /h- diploid cells carrying mat1-Pc induces a highly synchronized commitment to and execution of meiosis. Haploid or diploid pat1-114 mutants without mat1-Pc can also be used for convenience, although less synchrony may be attained compared with induction using true diploids. An essentially identical protocol can be used for induction via inhibition of genetically sensitized Pat1 kinase by ATP analogs.


15-deoxyspergualin primarily targets the trafficking of apicoplast proteins in Plasmodium falciparum.
15-Deoxyspergualin, an immunosuppressant with tumoricidal and antimalarial properties, has been implicated in the inhibition of a diverse array of cellular processes including polyamine synthesis and protein synthesis. Endeavoring to identify the mechanism of antimalarial action of this molecule, we examined its effect on Plasmodium falciparum protein synthesis, polyamine biosynthesis, and transport. 15-Deoxyspergualin stalled protein synthesis in P. falciparum through Hsp70 sequestration and subsequent phosphorylation of the eukaryotic initiation factor eIF2alpha. However, protein synthesis inhibition as well as polyamine depletion were invoked only by high micromolar concentrations of 15-deoxyspergualin, in contrast to the submicromolar concentrations sufficient to inhibit parasite growth. Further investigations demonstrated that 15-deoxyspergualin in the malaria parasite primarily targets the hitherto underexplored process of trafficking of nucleus-encoded proteins to the apicoplast. Our finding that 15-deoxyspergualin kills the malaria parasite by interfering with targeting of nucleus-encoded proteins to the apicoplast not only exposes a chink in the armor of the malaria parasite, but also reveals new realms in our endeavors to study this intriguing biological process.


Tuning the moenomycin pharmacophore to enable discovery of bacterial cell wall synthesis inhibitors.
New antibiotic drugs need to be identified to address rapidly developing resistance of bacterial pathogens to common antibiotics. The natural antibiotic moenomycin A is the prototype for compounds that bind to bacterial peptidoglycan glycosyltransferases (PGTs) and inhibit cell wall biosynthesis, but it cannot be used as a drug. Here we report the chemoenzymatic synthesis of a fluorescently labeled, truncated analogue of moenomycin based on the minimal pharmacophore. This probe, which has optimized enzyme binding properties compared to moenomycin, was designed to identify low-micromolar inhibitors that bind to conserved features in PGT active sites. We demonstrate its use in displacement assays using PGTs from S. aureus, E. faecalis, and E. coli. 110,000 compounds were screened against S. aureus SgtB, and we identified a non-carbohydrate based compound that binds to all PGTs tested. We also show that the compound inhibits in vitro formation of peptidoglycan chains by several different PGTs. Thus, this assay enables the identification of small molecules that target PGT active sites, and may provide lead compounds for development of new antibiotics.


Phenotypic selection varies with pollination intensity across populations of Sabatia angularis.
Pollinators are considered primary selective agents acting on plant traits, and thus variation in the strength of the plant-pollinator interaction might drive variation in the opportunity for selection and selection intensity across plant populations. Here, we examine whether these critical evolutionary parameters covary with pollination intensity across wild populations of the biennial Sabatia angularis. We quantified pollination intensity in each of nine S. angularis populations as mean stigmatic pollen load per population. For female fitness and three components, fruit number, fruit set (proportion of flowers setting fruit) and number of seeds per fruit, we evaluated whether the opportunity for selection varied with pollination intensity. We used phenotypic selection analyses to test for interactions between pollination intensity and selection gradients for five floral traits, including flowering phenology. The opportunity for selection via fruit set and seeds per fruit declined significantly with increasing pollen receipt, as expected. We demonstrated significant directional selection on multiple traits across populations. We also found that selection intensity for all traits depended on pollination intensity. Consistent with general theory about the relationship between biotic interaction strength and the intensity of selection, our study suggests that variation in pollination intensity drives variation in selection across S. angularis populations.


A practical approach to ultrasound of cervical lymph nodes.
Although the role of high resolution ultrasound (US) in evaluating cervical nodes is well established, it is often combined with fine needle aspiration cytology (FNAC). As a result, US appearances that help in distinguishing the various causes of cervical adenopathy are often overlooked and not emphasized. The aim of this study is to re-emphasize to the sonologist the US clues that may help in differentiating the aetiology of abnormal cervical nodes. We, therefore, present the spectrum of US appearances of lymph nodes. One hundred and forty patients (702 abnormal nodes) with known pathology were compared with 100 normal subjects (1211 nodes). After identifying an abnormal nodes, US features that further help in distinguishing between the various pathologies are the distribution of lymphadenopathy, echogenicity, calcification, distal enhancement, intranodal cystic necrosis, matting and soft tissue oedema.


Celastrol inhibits IL-1β-induced inflammation in orbital fibroblasts through the suppression of NF-κB activity.
Graves' disease is an autoimmune disease of the thyroid gland, which is characterized by hyperthyroidism, diffuse goiter and Graves' ophthalmopathy (GO). Although several therapeutic strategies for the treatment of GO have been developed, the effectiveness and the safety profile of these therapies remain to be fully elucidated. Therefore, examination of novel GO therapies remains an urgent requirement. Celastrol, a triterpenoid isolated from traditional Chinese medicine, is a promising drug for the treatment of various inflammatory and autoimmune diseases. CCK‑8 and apoptosis assays were performed to investigate cytotoxicity of celastrol and effect on apoptosis on orbital fibroblasts. Reverse transcription‑polymerase chain reaction, western blotting and ELISAs were performed to examine the effect of celastrol on interleukin (IL)‑1β‑induced inflammation in orbital fibroblasts from patients with GO. The results demonstrated that celastrol significantly attenuated the expression of IL‑6, IL‑8, cyclooxygenase (COX)‑2 and intercellular adhesion molecule‑1 (ICAM‑1), and inhibited IL‑1β‑induced increases in the expression of IL‑6, IL‑8, ICAM‑1 and COX‑2. The levels of prostaglandin E2 in orbital fibroblasts induced by IL‑1β were also suppressed by celastrol. Further investigation revealed that celastrol suppressed the IL‑1β‑induced inflammatory responses in orbital fibroblasts through inhibiting the activation of nuclear factor (NF)‑κB. Taken together, these results suggested that celastrol attenuated the IL‑1β‑induced pro‑inflammatory pathway in orbital fibroblasts from patients with GO, which was associated with the suppression of NF-κB activation.


Primary stenting of an unprotected left main coronary artery total occlusion in a patient with acute myocardial infraction and cardiogenic shock.
Acute total occlusion of the left main coronary artery (LMCA) is a rare angiographic finding with very poor prognosis. We report a case of a 39-year-old man who presented with pulmonary edema and cardiogenic shock due to an acute anterior myocardial infarction. Coronary angiography, which was performed under the support of an intra-aortic balloon pump, revealed total occlusion of the LMCA. Prompt and successful percutaneous transluminal coronary angioplasty with sirolimus-stent deployment in the LMCA allowed for an uneventful recovery and discharge of the patient.


Transmission of SARS-CoV-2 in Norwegian schools during academic year 2020-21: population wide, register based cohort study.
To assess the risk of transmission of SARS-CoV-2 in schools in Norway mainly kept open during the covid-19 pandemic in the academic year 2020-21. Population wide, register based cohort study. Primary and lower secondary schools in Norway open during the academic year 2020-21, with strict infection prevention and control measures in place, such as organisation of students into smaller cohorts. Contact tracing, quarantine, and isolation were also implemented, and testing of students and staff identified as close contacts. All students and educational staff in primary and lower secondary schools in Norway, from August 2020 to June 2021. Overall attack rate of SARS-CoV-2 transmission (AR14) was defined as the number of individuals (among students, staff, or both) in the school with covid-19, detected within 14 days of the index case, divided by the number of students and staff members in the school. AR14 to students (attack rates from all index cases to students only) and AR14 to school staff (attack rates from all index cases to staff members only) were also calculated. These measures for student and school staff index cases were also calculated separately to explore variation in AR14 based on the characteristics of the index case. From August 2020 to June 2021, 4078 index cases were identified; 3220 (79%) students and 858 (21%) school staff. In most (2230 (55%)) schools with an index case, no subsequent individuals with covid-19 were found within 14 days; in 631 (16%) schools, only one more individual with covid-19 within 14 days was found. Overall, AR14 was 0.33% (95% confidence interval 0.32% to 0.33%). When restricting index cases and subsequent individuals with covid-19 to students born in the same year, AR14 to students (0.56-0.78%) was slightly higher. Regarding the number of people infected with SARS-CoV-2 among students and staff, these results suggest that schools were not an important setting for transmission of the virus in Norway during the covid-19 pandemic in the academic year 2020-21.


Superoxidized states of Escherichia coli sulfite reductase heme protein subunit.
The oxidized forms of resting and sulfite-complexed Escherichia coli sulfite reductase heme protein subunit react with near-stoichiometric amounts of porphyrexide to produce what is best characterized as a ferrisiroheme pi cation radical. Addition of either sodium ascorbate or NADPH completely regenerates the parent form. Implications of these findings with respect to mechanisms of metal-radical J coupling and catalysis are discussed.


A Novel N-Methyltransferase in Arabidopsis Appears to Feed a Conserved Pathway for Nicotinate Detoxification among Land Plants and Is Associated with Lignin Biosynthesis.
The Preiss-Handler pathway, which salvages nicotinate (NA) for NAD synthesis, is an indispensable biochemical pathway in land plants. Various NA conjugations (mainly methylation and glycosylation) have been detected and have long been proposed for NA detoxification in plants. Previously, we demonstrated that NA O-glucosylation functions as a mobilizable storage form for NAD biosynthesis in the Brassicaceae. However, little is known about the functions of other NA conjugations in plants. In this study, we first found that N-methylnicotinate is a ubiquitous NA conjugation in land plants. Furthermore, we functionally identified a novel methyltransferase (At3g53140; NANMT), which is mainly responsible for N-methylnicotinate formation, from Arabidopsis (Arabidopsis thaliana). We also established that trigonelline is a detoxification form of endogenous NA in plants. Combined phylogenetic analysis and enzymatic assays revealed that NA N-methylation activity was likely derived from the duplication and subfunctionalization of an ancestral caffeic acid O-methyltransferase (COMT) gene in the course of land plant evolution. COMT enzymes, which function in S-lignin biosynthesis, also have weak NANMT activity. Our data suggest that NA detoxification conferred by NANMT and COMT might have facilitated the retention of the Preiss-Handler pathway in land plants.


Toxoplasma seroprevalence in healthy voluntary blood donors from urban Karnataka.
Although many infections can be transmitted through blood transfusion, it is not possible to carry out screening tests for all. Among the protozoal diseases transmitted by blood transfusion in India the most important is malaria, followed by toxoplasmosis. Screening for malaria is mandatory in India. We evaluated the seroprevalence of Toxoplasma gondii in healthy adult population of blood donors in Karnataka, south India. A total of 1000 serum samples collected in two batches (500 each) in the years 2004 and 2005 from healthy voluntary blood donors were tested for T. gondii antibodies by ELISA method, in addition to the other five mandatory tests. Overall 20.3 per cent were positive for T. gondii IgG antibody, of which, 63 per cent had high and 7 per cent low avidity, 3.6 per cent IgM positive. IgG titre ranged from 18-362 IU/ml. Our study showed a high prevalence of T. gondii antibodies in healthy voluntary blood population. It may be appropriate to include screening for T. gondii also in the pretransfusion blood testing schedule.


Glucose sensor based on glucose oxidase-lipid LB film immobilized in Prussian Blue layer.
The structure and dynamic organization of a mixed Langmuir film of glucose oxidase (GOx) and lipid at the air-water interface were studied. The film was transferred onto the Prussian Blue (PB)-modified Pt electrode for biosensor preparation. The PB modified electrode showed well defined redox peaks in 0.1 M PBS electrolyte. The Langmuir film was characterized at the air-water interface by pi-A isotherms. The mixed monolayer was formed by spreading GOx on the LB trough covered with lipid. Time-pressure results show that at least 90 minutes are required to reach the equilibrium state of GOx-lipid film. The monolayer was transferred onto the PB-modified electrode when surface pressure was 40 mN/m. This sensor was characterized by a very low detection limit and a wide linear range. The optimal conditions for both fabricating and response of the sensor were investigated. The proposed biosensor showed a linear calibration range from 5 x 10(-6) to 6 x 10(-5) M. The detection limit was determined to be 1.5 x 10(-6) M.


Experimental analysis to utilize the solid wastes in brick production.
Utilization of industrial, municipal, agricultural and other waste products in the industry has been the focus of research for economical, environmental, and technical reasons. Two solid wastes, i.e. Sugar-cane bagasse--is a fibrous waste-product of the sugar refining industry and granite processing industry generates a large amount of wastes mainly in the form of powder during sawing and polishing processes, which pollute and damage the environment, have been taken to experimental study. The objective of this study is to utilize the bagasse ash and granite waste for the manufacturing of bricks. Mixtures were prepared with 0, 10, 20, 30, 40 and 50% wastes of total weight of clay. The produced bricks are tested for mechanical properties, such as water absorption and compressive strength, according to Indian Standard Code. The result showed that 20% of bagasse ash and granite waste is optimum percentage to be used in the manufacturing of conventional bricks.


Prodding tardy reviewers: a randomized comparison of telephone, fax, and e-mail.
To compare telephone, fax, and e-mail methods of prodding tardy reviewers. Randomized trial conducted January 1998 through June 1999 at the main editorial office of Obstetrics & Gynecology. Reviewers who had failed to file reviews by 28 days after being sent manuscripts (7 days after deadline) were sent identical messages in oral (telephone) or written (fax and e-mail) form inquiring as to the status of review, asking for its completion as soon as possible, and requesting it be sent by fax or e-mail. Of 378 reviewers, proportions returning reviews within 7 days were essentially identical: telephone, 85 (68%) of 125; fax, 86 (67%) of 129; and e-mail, 84 (67%) of 124 (P =.59). In the two thirds who responded, the mean time to return reviews did not differ among the 3 groups. Contacting tardy reviewers resulted in a review being received within 7 days in about two thirds of cases, and it made no difference if the contact was made by telephone, fax, or e-mail.


Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study.
Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes. This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration. Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively. MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury. Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.


Asthma in Hispanics.
Hispanic individuals trace their ancestry to countries that were previously under Spanish rule, including Mexico, large parts of Central and South America, and some Caribbean islands. Most--but not all--Hispanics have variable proportions of European, Amerindian, and African ancestry. Hispanics are diverse with regard to many factors, including racial ancestry, country of origin, area of residence, socioeconomic status, education, and access to health care. Recent findings suggest that there is marked variation in the prevalence, morbidity, and mortality of asthma in Hispanics in the United States and in Hispanic America. The reasons for differences in asthma and asthma morbidity among and within Hispanic subgroups are poorly understood but are likely due to the interaction between yet-unidentified genetic variants and other factors, including environmental tobacco smoke exposure, obesity, allergen exposure, and availability of health care. Barriers to optimal management of asthma in Hispanics in the United States and in Hispanic America include inadequate access to health care, suboptimal use of antiinflammatory medications, and lack of reference values for spirometric measures of lung function in many subgroups (e.g., Puerto Ricans). Future studies of asthma in Hispanics should include large samples of subgroups that are well characterized with regard to self-reported ethnicity, country of origin, place of birth, area of residence, and indicators of socioeconomic status. Because Hispanics are disproportionately represented among the poor in the United States, implementation of adequate access to health care and social reforms (e.g., improving housing conditions) would likely have a major impact on reducing asthma morbidity in this population.


The fabrication of long-range ordered nanocrescent structures based on colloidal lithography and parallel imprinting.
A method for fabricating nanocrescent structures is presented based on a combination of colloidal lithography and parallel imprinting. In this process, non-close-packed colloidal spheres were prepared by a simple lift-up soft lithography technique, and subsequently the individual particles were used as shadow masks to angle deposit a layer of silver on the silicon substrates. Then, the silver-coated samples were etched to get silicon crescent nanohole arrays, which served as templates to mold patterned photocurable resin membranes. The patterned photocurable resin membranes were used to print gold nanocrescent nanostructures onto glass substrates. The size of the opening and the width of the gold nanostructures could be freely adjusted by changing the azimuth angle and tilt angle. Very importantly, the central angle of the nanocrescents could be adjusted in the range of 0°-360°. This method provides a low-cost and highly reproducible way to prepare complex nanostructure arrays for applications related to near field enhancement materials, optical sensors and surface-enhanced Raman spectroscopy, etc.


Diagnostic value of the LH-releasing hormone stimulation test in functional amenorrhea.
LH-releasing hormone (25 mug, iv.) was administered to 37 women with functional amenorrhea. In addition to the clinical classification, these patients were divided into three groups according to the basal level of serum LH. A significant correlation was found between the base-line levels of LH and the serum concentration of oestradiol plus oestrone. The absolute increment of LH after the injection of LH-RH was found to be dependent only on the base-line level of LH. Except for the patients with anorexia nervoxa, the base-line levels and the response pattern of FSH were almost the same for all three groups. From the results of this study, it was concluded that: 1. The circulating levels of oestradiol and oestrone, where derived from ovarian secretion, actually depend on the gonadotrophic stimulus. In patients with functional amenorrhea, the oestrogens do not make an independent contribution to the pituitary response to LH-RH. 2. Dysregulation of releasing hormones, whether located at the hypothalamic or suprahypothalamic level, necessarily influences the secretory capacity of the pituitary gland; long-standing deficiency of LH-RH, may finally lead to a state of pituitary "functional" unresponsiveness to releasing hormones. 3. In view of the excellent correlation between base-line levels of LH and the absolute increment of LH following stimulation with LH-RH, this test only accentuates the existing pituitary secretroy capacity, which can be roughly estimated from circulating levels of LH and FSH. 4. This test may be useful in distinguishing the milder cases of psychogenic amenorrhea from extreme gonadotrophic dysfunction in patients with anorexia nervosa.


Prostate-specific antigen in prostatic carcinoma.
To evaluate the clinical and prognostic value of prostate-specific antigen (PSA) for the detection of tumor and tumor growth after therapy, 520 sera from 246 patients with prostatic carcinoma, 990 sera from patients with BPH, and 1,488 sera from patients with other urological diseases were analyzed. The values ranged from 0.1 to 1,828.9 ng/ml. 51% of all values were about 2.5 ng/ml, and 76.8% of all values about 10 ng/ml. The commercial recommendation for the cutoff values is 2.5 ng/ml (IBL, FRG). In patients with benign prostatic hypertrophy this cutoff means 61% false-positive results, which makes the test highly sensitive but unspecific. In prostatic carcinoma patients this borderline means a false-negative result in 9.75% (24 of 246). By determining the cutoff at 10 ng/ml in our series, a false-negative result appeared in 14.6%. Therefore a plea is made for the 10-ng/ml cutoff. In follow-up studies a marked decline in PSA values after transurethral resection or antiandrogen therapy (orchiectomy/Zoladex/ICI/flutamide, Essex). Generally, the greater the PSA levels the more advanced the stage of disease. These data suggest that PSA may be a useful adjuvant marker for monitoring tumor growth in patients with regionally confined tumor.


Accurate Precursor Mass Assignment Improves Peptide Identification in Data-Independent Acquisition Mass Spectrometry.
Proteomics research today no longer simply seeks exhaustive protein identification; increasingly, it is also desirable to obtain robust, large-scale quantitative information. To accomplish this, data-independent acquisition (DIA) has emerged as a promising strategy largely owing to developments in advanced mass spectrometers and sophisticated data analysis methods. Nevertheless, the highly complex multiplexed MS/MS spectra produced by DIA remain challenging to interpret. Here, we present a novel strategy to analyze DIA data, based on unambiguous precursor mass assignment through the mPE-MMR (multiplexed post-experimental monoisotopic mass refinement) procedure and combined with complementary multistage database searching. Compared to conventional spectral library searching, the accuracy and sensitivity of peptide identification were significantly increased by incorporating precise precursor masses in DIA data. We demonstrate identification of additional peptides absent from spectral libraries, including sample-specific mutated peptides and post-translationally modified peptides using MS-GF+ and MODa/MODi multistage database searching. This first use of unambiguously determined precursor masses to mine DIA data demonstrates considerable potential for further exploitation of this type of experimental data.


Ultrasound-guided axillary nerve block for ED incision and drainage of deltoid abscess.
Deltoid abscesses are common and painful, often a consequence of injection drug use and seen frequently in emergency departments (EDs). The required incision and drainage can be completed successfully with effective pain relief using a peripheral nerve block. The brachial plexus nerve block works well, however it is technically complex with a low, but potentially serious, risk of complications such as phrenic nerve paralysis. Selective blockade of the axillary nerve eliminates the risks associated with a brachial plexus block, while providing more specific anesthesia for the deltoid region. Our initial experience suggests that the axillary nerve block (ANB) is a technically simple, safe, and effective way to manage the pain of deltoid abscesses and the necessary incision and drainage (I&D). The block involves using ultrasound guidance to inject a 20mL bolus of local anesthetic into the quadrangular space surrounding the axillary nerve (inferior to the posterolateral aspect of the acromion, near the overlap of the long head of triceps brachii and teres minor). Once injected the local will anesthetize the axillary nerve resulting in analgesia of the cutaneous area of the lateral shoulder and the deeper tissues including the deltoid muscle. Further research will clarify questions about the volume and concentration of local anesthetic, the role of injected adjuncts, and expected duration of analgesia and anesthesia. Herein we present a description of an axillary nerve block successfully used for deltoid abscess I&D in the ED.


Remodeling the dentofacial skeleton: the biological basis of orthodontics and dentofacial orthopedics.
Orthodontic tooth movement is dependent upon the remodeling of the periodontal ligament and alveolar bone by mechanical means. Facial sutures are also fibrous articulations, and by remodeling these joints, one can alter the positional relationships of the bones of the facial skeleton. As might be expected from the structure and mobility of the temporomandibular joint (TMJ), this articulation is more resistant to mechanical deformation, and whether functional mandibular displacement can alter the growth of the condyle remains controversial. Clinical investigations of the effects of the Andresen activator and its variants on dentofacial growth suggest that the changes are essentially dento-alveolar. However, with the popularity of active functional appliances, such as the Herbst and twin-block based on 'jumping the bite', attention has focused on how they achieve dentofacial change. Animal experimentation enables informed decisions to be made regarding the effects of orthodontic treatment on the facial skeleton at the tissue, cellular, and molecular levels. Both rat and monkey models have been widely used, and the following conclusions can be drawn from such experimentation: (1) Facial sutures readily respond to changes in their mechanical environment; (2) anterior mandibular displacement in rat models does not increase the mitotic activity of cells within the condyle to be of clinical significance, and (3) mandibular displacement in non-human primates initiates remodeling activity within the TMJ and can alter condylar growth direction. This last conclusion may have clinical utility, particularly in an actively growing child.


Enhancement of activities of anti-tumor drugs by dipyridamole against multidrug-resistant human hepatoma PLC/PRF/5 cells.
Dipyridamole (DPM) at 10 microM enhanced the cytotoxicity of anti-tumor drugs, which were associated with multidrug resistance, more in multidrug-resistant human hepatoma PLC/PRF/5 cells (PLC/COL) than in its parental cells (PLC/S). DPM increased, dose-dependently, the intracellular accumulation of [3H]vinblastine in PLC/COL. However, the effect was immediately diminished by its removal from the medium, indicating that DPM needed to be present together with the anti-tumor drugs to enhance the intracellular accumulation of the drugs. DPM inhibited the efflux of [3H]vinblastine from the PLC/COL cells, the binding of [3H]vinblastine to membrane vesicles of PLC/COL, and the binding of [3H]azidopine to P-glycoprotein in the plasma membrane of PLC/COL. Apparently DPM binds to P-glycoprotein and inhibits active efflux. [14C]labeled DPM was quickly incorporated into the cells and the cellular level of [14C]DPM reached a plateau after 5 min. It was slightly higher in PLC/S than in PLC/COL. The cellular [14C]DPM quickly disappeared after its removal from the medium. These results indicate that DPM binds quickly but reversibly to various kinds of cellular proteins including P-glycoprotein and inhibits active efflux of some anti-tumor drugs in multi-drug-resistant tumor cells, resulting in the enhancement of the activities of these drugs.


Comparison of Analytical Procedures in Method Transfer and Bridging Experiments.
Comparison of two analytical procedures is the primary objective of a method transfer or when replacing an old procedure with a new one in a single lab. Guidance for comparing two analytical procedures is provided in USP <1010> based on separate tests for accuracy and precision. Determination of criteria is somewhat problematic for these comparisons because of the interdependence of accuracy and precision. In this paper, a total error approach is proposed that requires a single criterion based on an allowable out-of-specification (OOS) rate at the receiving lab. This approach overcomes the difficulty of allocating acceptance criteria between precision and bias. Computations can be performed with any simulation software. Numerical examples are provided for four experimental designs that are typical in a method transfer study. Finally, recommendations are provided to help the user set criteria that provide an acceptable probability of passing for practical sample sizes.


Nucleotide synthetase ribozymes may have emerged first in the RNA world.
Though the "RNA world" hypothesis has gained a central role in ideas concerning the origin of life, the scenario concerning its emergence remains uncertain. It has been speculated that the first scene may have been the emergence of a template-dependent RNA synthetase ribozyme, which catalyzed its own replication: thus, "RNA replicase." However, the speculation remains uncertain, primarily because of the large sequence length requirement of such a replicase and the lack of a convincing mechanism to ensure its self-favoring features. Instead, we propose a nucleotide synthetase ribozyme as an alternative candidate, especially considering recent experimental evidence suggesting the possibility of effective nonenzymatic template-directed synthesis of RNA. A computer simulation was conducted to support our proposal. The conditions for the emergence of the nucleotide synthetase ribozyme are discussed, based on dynamic analysis on a computer. We suggest the template-dependent RNA synthetase ribozyme emerged later, perhaps after the emergence of protocells.


Social Determinants Associated with Pediatric Burn Injury: A Population-Based, Case-Control Study.
Social determinants of health (SDoH) influence risk of injury. We conducted a population-based, case-control study to identify which social determinants influence burn injury in children. Children (≤16 years of age) admitted to a Canadian regional burn center between January 1, 1999 and March 30, 2017 were matched based on age, sex, and geographic location 1:5 with an uninjured control cohort from the general population. Population-level administrative data describing the SDoH at the Manitoba Center for Health Policy (MCHP) were compared between the cohorts. Specific SDoH were chosen based on a published systematic review conducted by the research team. In the final multivariable model, children from a low-income household odds ratio (OR) (95% confidence interval) 1.97 (1.46, 2.65), in care 1.57 (1.11, 2.21), from a family that received income assistance 1.71 (1.33, 2.19) and born to a teen mother 1.43 (1.13, 1.81) were significantly associated with an increased risk of pediatric burn injury. This study identified SDoH that are associated with an increased risk of burn injury. This case-control study supports the finding that children from a low-income household, children in care, from a family that received income assistance, and children born to a teen mother are at an elevated risk of burn injury. Identifying children at increased potential risk allows targeting of burn risk reduction and home safety programs.


Exploring Genomic Variants Related to Residual Feed Intake in Local and Commercial Chickens by Whole Genomic Resequencing.
Improving feed efficiency is a major goal in poultry production to reduce production costs and increase profitability. The genomic variants and possible molecular mechanisms responsible for residual feed intake (RFI) in chickens, however, remain poorly understood. In this study, using both local and commercial breeds, genome re-sequencing of low RFI and high RFI chickens was performed to elucidate the genomic variants underlying RFI. Results showed that 8,505,214 and 8,479,041 single nucleotide polymorphisms (SNPs) were detected in low and high RFI Beijing-You chickens, respectively; 8,352,008 and 8,372,769 SNPs were detected in low- and high-RFI Cobb chickens, respectively. Through a series of filtering processes, 3746 candidate SNPs assigned to 1137 genes in Beijing-You chickens and 575 candidate SNPs (448 genes) in Cobb chickens were found. The validation of the selected 191 SNPs showed that 46 SNPs were significantly associated with the RFI in an independent population of 779 Cobb chickens, suggesting that the method of screening associated SNPs with whole genome sequencing (WGS) strategy was reasonable. Functions annotation of RFI-related genes indicated that genes in Beijing-You were enriched in lipid and carbohydrate metabolism, as well as the phosphatase and tensin homolog (PTEN) signaling pathway. In Cobb, however, RFI-related genes were enriched in the feed behavior process and cAMP responsive element binding protein (CREB) signaling pathway. For both breeds, organismal development physiological processes were enriched. Correspondingly, NOS1, PHKG1, NEU3 and PIP5K1B were differentially expressed in Beijing-You, while CDC42, CSK, PIK3R3, CAMK4 and PLCB4 were differentially expressed in Cobb, suggesting that these might be key genes that contribute to RFI. The results of the present study identified numerous novel SNPs for RFI, which provide candidate biomarkers for use in the genetic selection for RFI. The study has improved knowledge of the genomic variants and potential biological pathways underlying RFI in chickens.


Infant discrimination of faces in naturalistic events: actions are more salient than faces.
Despite the fact that faces are typically seen in the context of dynamic events, there is little research on infants' perception of moving faces. L. E. Bahrick, L. J. Gogate, and I. Ruiz (2002) demonstrated that 5-month-old infants discriminate and remember repetitive actions but not the faces of the women performing the actions. The present research tested an attentional salience explanation for these findings: that dynamic faces are discriminable to infants, but more salient actions compete for attention. Results demonstrated that 5-month-old infants discriminated faces in the context of actions when they had longer familiarization time (Experiment 1) and following habituation to a single person performing 3 different activities (Experiment 2). Further, 7-month-old infants who have had more experience with social events also discriminated faces in the context of actions. Overall, however, discrimination of actions was more robust and occurred earlier in processing time than discrimination of dynamic faces. These findings support an attentional salience hypothesis and indicate that faces are not special in the context of actions in early infancy.


Quantifying chain reptation in entangled polymer melts: topological and dynamical mapping of atomistic simulation results onto the tube model.
The topological state of entangled polymers has been analyzed recently in terms of primitive paths which allowed obtaining reliable predictions of the static (statistical) properties of the underlying entanglement network for a number of polymer melts. Through a systematic methodology that first maps atomistic molecular dynamics (MD) trajectories onto time trajectories of primitive chains and then documents primitive chain motion in terms of a curvilinear diffusion in a tubelike region around the coarse-grained chain contour, we are extending these static approaches here even further by computing the most fundamental function of the reptation theory, namely, the probability psi(s,t) that a segment s of the primitive chain remains inside the initial tube after time t, accounting directly for contour length fluctuations and constraint release. The effective diameter of the tube is independently evaluated by observing tube constraints either on atomistic displacements or on the displacement of primitive chain segments orthogonal to the initial primitive path. Having computed the tube diameter, the tube itself around each primitive path is constructed by visiting each entanglement strand along the primitive path one after the other and approximating it by the space of a small cylinder having the same axis as the entanglement strand itself and a diameter equal to the estimated effective tube diameter. Reptation of the primitive chain longitudinally inside the effective constraining tube as well as local transverse fluctuations of the chain driven mainly from constraint release and regeneration mechanisms are evident in the simulation results; the latter causes parts of the chains to venture outside their average tube surface for certain periods of time. The computed psi(s,t) curves account directly for both of these phenomena, as well as for contour length fluctuations, since all of them are automatically captured in the atomistic simulations. Linear viscoelastic properties such as the zero shear rate viscosity and the spectra of storage and loss moduli obtained on the basis of the obtained psi(s,t) curves for three different polymer melts (polyethylene, cis-1,4-polybutadiene, and trans-1,4-polybutadiene) are consistent with experimental rheological data and in qualitative agreement with the double reptation and dual constraint models. The new methodology is general and can be routinely applied to analyze primitive path dynamics and chain reptation in atomistic trajectories (accumulated through long MD simulations) of other model polymers or polymeric systems (e.g., bidisperse, branched, grafted, etc.); it is thus believed to be particularly useful in the future in evaluating proposed tube models and developing more accurate theories for entangled systems.


Evaluation of the Diagnostic Performance of mNGS in Detecting Intra-Abdominal Infections of the Emergency Department Patients.
Intra-abdominal infections (IAI) are gradually becoming common in the emergency department, though the incidence is low and the prognosis is fair, as the symptoms are similar to other intra-abdominal diseases, rapid and accurate diagnosis of the causative agents is essential for clinical management. This study aimed to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) in detecting IAI in the emergency department. This was a retrospective, single-centered study including patients admitted to the emergency department from January 1st, 2021 to August 31st, 2022 with diagnosis of IAI. The comparison between mNGS and microbial culture using paracentesis fluid samples was performed to evaluate the diagnostic performance of mNGS for IAI. Meanwhile, paracentesis fluid and peripheral blood mNGS were compared to explore the sample specificity. Further, the microbial community structure of the patients with pyogenic liver abscesses (PLA) was analyzed. Thirty-four IAI patients including 23 with pyogenic liver abscesses (PLA), 3 with parapancreatic abscesses, and 8 with other IAI were included in this study. Compared with the conventional microbial culture of paracentesis fluid, mNGS using paracentesis fluid detected more positive cases of IAI (93.75% vs 81.25%), and identified more species of pathogens, especially in obligate anaerobes and viral pathogens. Peripheral blood mNGS presented a relatively high consistency with the paracentesis fluid mNGS (91% mutual positive). The microbial community structure of PLA patients with diabetes is less diverse than that of those without diabetes. Patients with diabetes are at high risk of PLA caused by Klebsiella pneumonia. mNGS has advantages in detecting IAI in the emergency department, and peripheral blood mNGS can be a non-invasive choice for early diagnosis.


Otorhinolaryngological manifestations of von Recklinghausen's disease in Nigerians.
Otorhinolaryngological manifestations of 13 patients with von Recklinghausen's disease appearing at Lagos University Teaching Hospital over a five-year period have been studied. Among patients with ENT manifestations of the disease, the most common general features exhibited were cutaneous neurofibromas (100 per cent), headache (69.23 per cent) and pruritus (46.15 per cent). But the head and neck findings included external meatal canal stenosis (30.77 per cent), conductive deafness (30.77 per cent), nasal discharge (30.77 per cent), cranial nerve involvement (30.77 per cent) and disfigurement of the soft tissues of the face (30.77 per cent). Involvement of pinna (23.31 per cent), rhinolalia aperta (15.38 per cent), mental retardation (15.38 per cent) and pharyngeal swelling (7.69 per cent) also featured. Clinically detectable bilateral acoustic neurofibromas in adults or astrocytomas in children were not found in this series. Involvement of the frontoparietal bone (7.65 per cent) presented with skull bossing which had to be differentiated from that due to sickle cell disease in the African. There was also a singular case of phrenic nerve involvement. However, malignancy occurred in one (7.69 per cent) of these patients. Thus, it is important always to follow-up these patients closely so as to detect malignant transformation in time.


Studies on the effects of the spillway on the occlusal table of complete dentures upon the bearing of masticatory force.
We studied the effect of spillways in the posterior artificial teeth of complete dentures in reducing masticatory pressure on the basal mucosa by making completely edentulous patients masticate food. Using two kinds of experimental dentures, one with spillways on the occlusal table and the other without, five subjects wearing complete dentures were instructed to masticate four different types of test food. The results showed that the mastication time and the number of masticatory strokes were not much affected by the existence of spillways. However, the masticatory force of artificial teeth with spillways was slightly smaller than that of artificial teeth without spillways.


Penalized Estimating Functions and Variable Selection in Semiparametric Regression Models.
We propose a general strategy for variable selection in semiparametric regression models by penalizing appropriate estimating functions. Important applications include semiparametric linear regression with censored responses and semiparametric regression with missing predictors. Unlike the existing penalized maximum likelihood estimators, the proposed penalized estimating functions may not pertain to the derivatives of any objective functions and may be discrete in the regression coefficients. We establish a general asymptotic theory for penalized estimating functions and present suitable numerical algorithms to implement the proposed estimators. In addition, we develop a resampling technique to estimate the variances of the estimated regression coefficients when the asymptotic variances cannot be evaluated directly. Simulation studies demonstrate that the proposed methods perform well in variable selection and variance estimation. We illustrate our methods using data from the Paul Coverdell Stroke Registry.


Development and validation of sensitive LC-MS/MS method for the quantification of SUVN-502 and its metabolite and its application for first in human pharmacokinetic study.
A sensitive and rapid LC-MS/MS method was developed and validated for the quantification of SUVN-502 and M1 of SUVN-502, a 5-HT6 receptor antagonist for the treatment of dementia associated with Alzheimer's disease. Following solid-phase extraction, SUVN-502 and M1 of SUVN-502 and IS were eluted with 10mM ammonium acetate (pH 4.0) and acetonitrile using a rapid gradient program on reverse phase column. Multiple reaction monitoring mode was used to monitor the respective transitions of m/z 478.2→377.7 for SUVN-502 and m/z 464.1→377.7 for M1 of SUVN-502. The assay exhibited a linear dynamic range of 10-10000pg/mL for SUVN-502 and 20-20000pg/mL for M1 of SUVN-502 in human plasma. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The within batch accuracy and precision were within acceptable limits. All the other validation parameters were within the acceptable limits. The validated method was applied to analyze human plasma samples obtained from a human pharmacokinetic study consisting single and multiple ascending doses.


Multifunctional organic-inorganic hybrid nanoparticles and nanosheets based on chitosan derivative and layered double hydroxide: cellular uptake mechanism and application for topical ocular drug delivery.
To study the cellular uptake mechanism of multifunctional organic-inorganic hybrid nanoparticles and nanosheets, new chitosan-glutathione-valine-valine-layered double hydroxide (CG-VV-LDH) nanosheets with active targeting to peptide transporter-1 (PepT-1) were prepared, characterized and further compared with CG-VV-LDH nanoparticles. Both organic-inorganic hybrid nanoparticles and nanosheets showed a sustained release in vitro and prolonged precorneal retention time in vivo, but CG-VV-LDH nanoparticles showed superior permeability in the isolated cornea of rabbits than CG-VV-LDH nanosheets. Furthermore, results of cellular uptake on human corneal epithelial primary cells (HCEpiC) and retinal pigment epithelial (ARPE-19) cells indicated that both clathrin-mediated endocytosis and active transport of PepT-1 are involved in the internalization of CG-VV-LDH nanoparticles and CG-VV-LDH nanosheets. In summary, the CG-VV-LDH nanoparticle may be a promising carrier as a topical ocular drug delivery system for the treatment of ocular diseases of mid-posterior segments, while the CG-VV-LDH nanosheet may be suitable for the treatment of ocular surface diseases.


The temperature-dependence of rapid low temperature reactions: experiment, understanding and prediction.
Despite the success of the CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme) method in measuring rate coefficients for neutral-neutral reactions of radicals down close to the very low temperatures prevalent in dense interstellar clouds (ISCs), there are still many reactions of potential importance in the chemistry of these objects for which there have been no measurements of low temperature rate coefficients. One important class of reactions is that between atomic and molecular free radicals and unsaturated hydrocarbons; that is, alkynes and alkenes. Based on semi-empirical arguments and correlations of 'room temperature' rate coefficients, k(298 K), for reactions of this type with the difference between the ionisation energy of the alkyne/alkene and the electron affinity of the radical, we suggest which reactions between the radicals, C(3P), O(3P), N(4S), CH, C2H and CN, and carbon chain molecules (Cn) and cyanopolyynes (HC2nCN and NCC2nCN) are likely to be fast at the temperature of dense ISCs. These reactions and rate coefficients have been incorporated into a purely gas-phase model (osu2005) of ISC chemistry. The results of these calculations are presented and discussed.


A quantitative structure-activity relationship study of some substance P-related peptides. A multivariate approach using PLS and variable selection.
Nine new analogues of substance P (SP) were designed using quantitative sequence-activity models based on the amino acid z-scales with PLS as the statistical method and the GOLPE procedure for variable selection. The nine SP analogues were synthesised by solid-phase peptide synthesis and tested for affinity to the NK-1 receptor from rat brain with radio receptor assay using [125I]-Bolton-Hunter substance P as labelled ligand. All of the new substance P analogues showed high affinities, with IC50 values of less than 0.8 nM. One analog, Lys-Arg-Ala-Lys-Phe-Met-Met-Phe-Phe-Gly-Leu-Let-NH2, showed a exceptional high affinity for the NK1 receptor, with IC50 = 5 pM.


[Clinical efficacy of intra-articular parecoxib injection for the treatment of early knee osteoarthritis].
To observe and evaluate the clinical effect of intra-articular injection of parecoxib in patients with early knee osteoarthritis. From September 2016 to August 2017, 107 patients with early knee osteoarthritis were treated, including 50 males and 57 females, aged 45 to 64 (51.9±4.2) years. They were divided into basic therapy+oral glucosamine group(group A) 36 cases, oral celecoxib+basic therapy+oral glucosamine group(group B) 36 cases, intra-articular injection of parecoxib+basic therapy+oral glucosamine group(group C) 35 cases. There was no significant difference in gender, age, BMI and clinical stage(Kellgren-Lawrence classification) between the three groups before treatment. VAS score, HSS score and patient satisfaction were compared before and after treatment in the three groups. The levels of inflammatory cytokines in synovial fluid were measured before and after treatment in the three groups. All cases were followed up for(15.2±2.6) months on average. The VAS score and HSS score of each group were improved after treatment(P<0.001). There were significant differences in VAS and HSS scores among the three groups after treatment(P<0.001). The clinical efficacy of group C was better than that of group A and B(P<0.001), group B was better than that of group A(P<0.001), and group C had the highest satisfaction(P<0.001). After treatment, the concentration of proinflammatory factor TNF-α and IL-6 in the synovial fluid of each group decreased(P<0.001) and the concentration of anti-inflammatory factor IL-10 increased(P<0.001). After treatment, the concentrations of TNF-α, IL-6 and IL-10 in the synovial fluid of the three groups were significantly different(P<0.001). For patients with early knee osteoarthritis, intra-articular injection of parecoxib can significantly improve clinical symptoms and avoid adverse reactions of long-term oral NSAIDs, which is an effective treatment.


Voriconazole salvage treatment of invasive candidiasis.
Data on the salvage treatment of invasive candidiasis with voriconazole in 52 patients intolerant of other antifungal agents or with infection refractory to other antifungal agents were analyzed. Patients had received a mean of two previous antifungal agents (range, 1-4 agents), and 83% had received an azole. Manifestations of invasive candidiasis included candidemia (37%), disseminated disease (25%), and infection of other sites (38%). The median duration of voriconazole therapy was 60 days (range, 1-314 days). The overall rate of response was 56% (95%CI, 41-70), with the following response rates observed for individual Candida species: Candida albicans, 44% (20-70); Candida glabrata, 38% (14-68); Candida krusei, 70% (35-93); Candida tropicalis, 67% (30-93); and other Candida spp., 100% (40-100). The response rate in patients who had failed previous azole therapy was 58% (42-73). Common adverse events (~20%) included nausea and emesis, abnormal liver enzymes, and visual disturbances. Serious adverse events occurred in four patients, and nine patients died. Voriconazole has promise as a salvage agent for the treatment of invasive candidiasis, even in the settings of previous azole therapy and infection due to Candida krusei.


Image Formation in the Living Human Eye.
The human eye is a relatively simple optical instrument that imposes the first performance limits on the visual system. This review describes the main optical properties of the eye: geometric image formation, aberrations, and intraocular scattering. The article also discusses the sources of optical degradations and their impact on visual performance.


PKCα-mediated phosphorylation of LSD1 is required for presynaptic plasticity and hippocampal learning and memory.
Lysine-specific demethylase 1 (LSD1) is a histone demethylase that participates in transcriptional repression or activation. Recent studies reported that LSD1 is involved in learning and memory. Although LSD1 phosphorylation by PKCα was implicated in circadian rhythmicity, the importance of LSD1 phosphorylation in learning and memory is unknown. In this study, we examined the roles of LSD1 in synaptic plasticity and memory using Lsd1 SA/SA knock-in (KI) mice, in which a PKCα phosphorylation site is mutated. Interestingly, short-term and long-term contextual fear memory as well as spatial memory were impaired in Lsd1 KI mice. In addition, short-term synaptic plasticity, such as paired pulse ratio and post-tetanic potentiation was impaired, whereas long-term synaptic plasticity, including long-term potentiation and long-term depression, was normal. Moreover, the frequency of miniature excitatory postsynaptic current was significantly increased, suggesting presynaptic dysfunction in Lsd1 KI mice. Consistent with this, RNA-seq analysis using the hippocampus of Lsd1 KI mice showed significant alterations in the expressions of presynaptic function-related genes. Intriguingly, LSD1n-SA mutant showed diminished binding to histone deacetylase 1 (HDAC1) compared to LSD1n-WT in SH-SY5Y cells. These results suggest that LSD1 is involved in the regulation of presynaptic gene expression and subsequently regulates the hippocampus-dependent memory in phosphorylation-dependent manner.


Transcatheter closure of fossa ovalis atrial septal defect: a single institutional experience.
Transcatheter closure of the fossa ovalis atrial septal defect with adequate rims has become the procedure of choice in recent times. We report our experience with 439 patients who were selected for percutaneous device closure and 430 of whom underwent transcatheter closure of fossa ovalis atrial septal defects from May 1997 to May 2006. Device closure was not attempted in the remaining nine patients after initial evaluation due to high right atrial pressure following balloon occlusion (n=1 not parallel, high pulmonary vascular resistance (n=1), significant coronary artery disease (n=1), or the fact that the atrial septal defect was unsuitable for device closure (n=6). The anatomical size of the atrial septal defects ranged from 7-40 mm. Six patients underwent a combined procedure at the time of the atrial septal defect device closure (balloon pulmonary valvotomy in 4 cases, balloon pulmonary valvotomy and patent ductus arteriosus device closure in 1, and pulmonary ductus arteriosus coil closure in 1). The patients were in the age group of 2-77 years, the mean age being 20 years. Major complications occurred in seven cases. In 4 patients, there was device embolization immediately after deployment; there was left atrial appendage perforation, in one patient leading to cardiac tamponade during deployment of the device, and development of pulmonary edema in two patients. The cases in which device embolization took place underwent conventional surgery for atrial septal defect patch closure, while the patient with left atrial appendage perforation underwent emergency surgery (suturing of the left atrial appendage). Both patients with pulmonary edema were managed conservatively. The immediate success rate of device closure was 96.9%. All but one patient with multiple defects had no residual shunt at follow-up. On three months' to nine years' follow-up, the device remained stable, with no significant residual shunt and no history of thrombus formation on transthoracic echocardiography.


When "Patient-Centered" is Not Enough: A Call for Community-Centered Medicine.
Before entering medicine, I was inspired by community organizing as a model for driving social change and improving public health. As a clinician, I remain inspired by this approach; however, I find that it has been more challenging to integrate into my day-to-day work than I expected. In this essay, I describe my journey from community organizer to primary care clinician and reflect on the lessons I've learned about the value of community organizing and ways that it can be incorporated into clinical practice. Ultimately, I propose a model for how clinicians and health centers can proactively partner with community organizing groups and facilitate referrals to help patients directly engage in transforming the root causes of their health challenges. This model shifts the focus from the patient as an individual agent of change to the community, and offers important lessons to clinicians interested in community health equity.


The multi-target small-molecule inhibitor SB747651A shows in vitro and in vivo anticancer efficacy in glioblastomas.
Glioblastoma multiforme is the most common primary brain tumor and among the most lethal types of cancer. Several mono-target small molecule-inhibitors have been investigated as novel therapeutics, thus far with poor success. In this study we investigated the anticancer effects of SB747651A, a multi-target small-molecule inhibitor, in three well characterized patient-derived glioblastoma spheroid cultures and a murine orthotopic xenograft model. Concentrations of 5-10 µM SB747651A reduced cell proliferation, spheroid formation, migration and chemoresistance, while apoptotic cell death increased. Investigation of oncogenic kinase signaling showed decreased phosphorylation levels of mTOR, CREB, GSK3 and GYS1 leading to altered glycogen metabolism and formation of intracellular reactive oxygen species. Expression levels of cancer stemness marker SOX2 were reduced in treated tumor cells and SB747651A treatment significantly prolonged survival of mice with intracranial glioblastoma xenografts, while no adverse effects were observed in vivo at doses of 25 mg/kg administered 5 days/week for 8 weeks. These findings suggest that SB747651A has anticancer effects in glioblastoma. The cancer-related pathophysiological mechanisms targeted by SB747651A are shared among many types of cancer; however, an in-depth clarification of the mechanisms of action in cancer cells is important before further potential application of SB747651A as an anticancer agent can be considered.


A femoral arteriovenous shunt facilitates arterial whole blood sampling in animals.
In this study we evaluated on-line continuous blood sampling in a femoral arteriovenous (a-v) shunt for use in quantitative tracer studies using gamma-emitting radionuclides in animals. The shunt consisted of 40 cm polyethylene tubing (PE-50) guided through a coincidence probe. Two three-way valves allowed blood pressure measurements and tracer injection. Blood flow in the shunt and the impulse response function (IRF) were assessed using heparinized human blood mixed with fluorine-18 fluorodeoxyglucose (FDG). In vivo experiments were performed in eight male rats (300-350 g) anaesthetized with halothane. In three rats, manual blood sampling was performed in parallel with on-line sampling. In another five animals, the arterial whole blood activity was recorded on-line for 40 min. For the experiments 150-180 MBq FDG was injected over 35 s. Blood flow in the shunt was 23.6, 29.2 and 42.8 ml/h at 100, 120 and 160 mmHg, respectively. The IRF was characterized by minimal dispersion (1-2 s FWHM). Deconvolution of the measured arterial input curves with the IRF changed the measured curve only minimally. Whole blood radioactivity concentration derived from manual and on-line sampling were in excellent agreement. The curves derived from on-line sampling were of high statistical quality. In conclusion, a femoral a-v shunt allows multiple manipulations such as measurement of the arterial whole blood activity, continuous blood pressure monitoring, injection of the tracer and collection of blood samples if necessary. It is not associated with blood loss if the collection of blood samples is not required. It is more convenient to use than manual sampling, the peak of the input curve is never missed and the input curves are of high statistical quality.


The GABAA receptor and its antibodies.
The GABAA/benzodiazepine receptor has been purified to homogeneity from bovine and rat cerebral cortex. Under optimum conditions, the purified receptor has been shown to possess four distinct drug-binding sites, for GABA, benzodiazepine, barbiturate and Cl- channel gating classes of ligands. The receptor is a multi-subunit membrane glycoprotein with an oligomeric size of 230,000 Da. It contains at least two subunits, alpha and beta, the first of which can be photoaffinity-labelled with the benzodiazepine, flunitrazepam. Polyclonal and monoclonal antibodies have been raised to the native receptor and both have been used in an immunological characterization of the receptor protein in detergent extracts and likewise in purified preparations from bovine cerebral cortex.


Variability in diurnal testosterone, exposure to violence, and antisocial behavior in young adolescents.
The purpose of this report is to provide evidence of an association between within-person variability in diurnal testosterone over 1 year, lifetime exposure to violence, and the manifestation of antisocial behavior in 135 pubertal-aged adolescents across 1 year. Adolescents' sex and lifetime history of violence exposure moderated the association between within-person variability in diurnal testosterone and antisocial behavior. Furthermore, sex-stratified analyses revealed that lifetime history of exposure to violence moderated the association between within-person variability in diurnal testosterone and antisocial behavior in females only. This report is unique in that it illuminates sex differences in within-person associations among exposure to violence, individual variability in diurnal testosterone, and antisocial behavior.


Initial therapy, persistence and regimen change in a cohort of newly treated type 2 diabetes patients.
The aim was to describe the utilization of antidiabetic agents, in terms of persistence and regimen change, in the management of a cohort of newly treated type 2 diabetes patients and to investigate associated socio-demographic and treatment factors. A population-based retrospective cohort study was conducted using the national pharmacy claims database in Ireland. Subjects were analyzed for persistence and regimen change. Cox proportional hazards regression examined associations of socio-demographic and treatment factors on treatment patterns. Hazard ratios (HR) and 95% CIs are presented. A total of 20947 subjects were identified in the study over a 2 year period. Most were initiated on metformin (76%) or sulphonylureas (22%) and 77% were persistent with therapy 12 months after initiation. The likelihood of non-persistence was significantly lower in the youngest (40-49 years) age groups (reference 60-69 years) (HR 1.62, 95% CI 1.42, 1.84) and those on sulphonylureas (HR 1.49, 95% CI 1.36, 1.64). The likelihood of receiving a regimen change was significantly lower in the older (80+ years) age groups (HR 0.63, 95% CI 0.56, 0.71), females (HR 0.91, 95% CI 0.86, 0.95), and those with pre-existing CVD (1 vs. 0 CVD medicines) (HR 0.82, 95% CI 0.74, 0.90), and higher in those on sulphonylureas (HR 1.83, 95% CI 1.73, 1.94). Type of treatment, pre-existing CVD and demographic factors are shown to be associated with the observed treatment patterns. Guideline recommended agents were widely used on treatment initiation though a substantial minority were not initiated on the recommended first line agent. Use of guideline recommended agents was not as evident during treatment progression. Further optimization of initial and subsequent antidiabetic agent prescribing may be possible.


[Immunologic tolerance of anti-Abeta antibody in the sera of AD patients].
To characterize anti-amyloid-beta antibodies in the sera of Alzheimer's disease(AD) patients. A special tissue amyloid plaque immunoreactivity (TAPIR) examinations of brains of Tg2576 mice was carried out. Abeta(42)-GST fusion protein was detected by Western blot. and then the survival rate of PC12 cells incubated with the sera and Abeta(42) was measured by MTT assay. The sera in AD patients could not recognize the senile plaque in the brains of Tg2576 mice and could not cross-react with Abeta(42)-GST fusion protein. Furthermore, PC12 cells incubated with the sera from AD patients presented the decreased A value compared with the healthy elderly(P<0.01). The anti-Abeta antibodies in the sera of AD patients may have immunologic tolerance to amyloid peptide.


Shock tube investigation of CH3 + CH3OCH3.
The title reaction has been investigated in a diaphragmless shock tube by laser schlieren densitometry over the temperature range 1163-1629 K and pressures of 60, 120, and 240 Torr. Methyl radicals were produced by dissociation of 2,3-butanedione in the presence of an excess of dimethyl ether. Rate coefficients for CH(3) + CH(3)OCH(3) were obtained from simulations of the experimental data yielding the following expression which is valid over the range 1100-1700 K: k = (10.19 ± 3.0)T(3.78) exp((-4878/T)) cm(3) mol(-1)s(-1). The experimental results are in good agreement with estimates by Curran and co-workers [Fischer, S. L.; Dryer, F. L.; Curran, H. J. Int. J. Chem. Kinet.2000, 32 (12), 713-740. Curran, H. J.; Fischer, S. L.; Dryer, F. L. Int. J. Chem. Kinet.2000, 32 (12), 741-759] but about a factor of 2.6 lower than those of Zhao et al. [Zhao, Z.; Chaos, M.; Kazakov, A.; Dryer, F. L. Int. J. Chem. Kinet.2008, 40 (1), 1-18].


Renal failure and bacterial infections in patients with cirrhosis: epidemiology and clinical features.
The aim of the study was to investigate the prevalence and clinical course of renal failure that was induced by the various types of bacterial infections in patients with cirrhosis and ascites. Three hundred and nine patients, who were consecutively admitted to the 3 major hospitals of Padova, Italy, during the first 6 months of 2005, were studied prospectively. Of these, 233 patients (75.4%) had evidence of ascites. In 104 patients with cirrhosis and ascites (44.6%) a bacterial infection was diagnosed. A bacterial infection-induced renal failure was observed in 35 of 104 patients (33.6%). The prevalence of renal failure was higher in biliary or gastrointestinal tract infections and in spontaneous bacterial peritonitis (SBP) and in than in other types of infections. In addition, the progressive form of renal failure was only precipitated by biliary or gastrointestinal tract infections, SBP, and urinary tract infections (UTI). In a multivariate analysis only MELD score (P = 0.001), the peak count of neutrophil leukocyte in blood (P = 0.04), and the lack of resolution of infection (P = 0.03) had an independent predictive value on the occurrence of renal failure. The results of the study show that the development of bacterial-induced renal failure in patients with cirrhosis and ascites is related to the MELD score, and to both the severity and the lack of resolution of the infection. A progressive form of renal failure occurs only as a consequence of biliary or gastrointestinal tract infections, SBP, and UTI.


Ocular biometric correlates of ciliary muscle thickness in human myopia.
Anterior segment optical coherent tomography (AS-OCT) is used to further examine previous reports that ciliary muscle thickness (CMT) is increased in myopic eyes. With reference to temporal and nasal CMT, interrelationships between biometric and morphological characteristics of anterior and posterior segments are analysed for British-White and British-South-Asian adults with and without myopia. Data are presented for the right eyes of 62 subjects (British-White n = 39, British-South-Asian n = 23, aged 18-40 years) with a range of refractive error (mean spherical error (MSE (D)) -1.74 ± 3.26; range -10.06 to +4.38) and separated into myopes (MSE (D) <-0.50, range -10.06 to -0.56; n = 30) and non-myopes (MSE (D) ≥-0.50, -0.50 to +4.38; n = 32). Temporal and nasal ciliary muscle cross-sections were imaged using a Visante AS-OCT. Using Visante software, manual measures of nasal and temporal CMT (NCMT and TCMT respectively) were taken in successive posterior 1 mm steps from the scleral spur over a 3 mm distance (designated NCMT1, TCMT1 et seq). Measures of axial length and anterior chamber depth were taken with an IOLMaster biometer. MSE and corneal curvature (CC) measurements were taken with a Shin-Nippon auto-refractor. Magnetic resonance imaging was used to determine total ocular volume (OV) for 31 of the original subject group. Statistical comparisons and analyses were made using mixed repeated measures anovas, Pearson's correlation coefficient and stepwise forward multiple linear regression. MSE was significantly associated with CMT, with thicker CMT2 and CMT3 being found in the myopic eyes (p = 0.002). In non-myopic eyes TCMT1, TCMT2, NCMT1 and NCMT2 correlated significantly with MSE, AL and OV (p < 0.05). In contrast, myopic eyes failed generally to exhibit a significant correlation between CMT, MSE and axial length but notably retained a significant correlation between OV, TCMT2, TCMT3, NCMT2 and NCMT3 (p < 0.05). OV was found to be a significantly better predictor of TCMT2 and TCMT3 than AL by approximately a factor of two (p < 0.001). Anterior chamber depth was significantly associated with both temporal and nasal CMT2 and CMT3; TCMT1 correlated positively with CC. Ethnicity had no significant effect on differences in CMT. Increased CMT is associated with myopia. We speculate that the lack of correlation in myopic subjects between CMT and axial length, but not between CMT and OV, is evidence that disrupted feedback between the fovea and ciliary apparatus occurs in myopia development.


Age-associated C-cell hyperplasia in the human thyroid.
C cells in 26 normal human thyroids from forensic autopsies were identified by immunoperoxidase staining for calcitonin. C-cell concentrations and total C-cell numbers were determined with the use of morphometric techniques. There was great variation in C-cell density within a given gland and among individuals, although C cells tended to concentrate about one third of the way down the vertical axis of the lateral lobes. Densities of 1-2000 cells/cu mm were found in the third and later decades. In addition there was a statistically significant (P less than 0.01) positive Spearman correlation between total C-cell numbers and age in males. C-cell hyperplasia appears to be an age-related phenomenon that may have physiologic significance and must be taken into consideration in evaluation of thyroid glands for the diagnosis of premalignant lesions of C cells.


Survival following intentional massive overdose of 'Ecstasy'.
A case of intentional overdose with 18 'Ecstasy' tablets is described. 'Ecstasy' is a semi-synthetic hallucinogenic amphetamine and acute adverse reactions follow from the effects of sympathetic stimulation. To our knowledge this is the first reported case of massive intentional overdose reported in the literature.